Leite Sérgio Carvalho, Sampaio Paula, Sousa Vera Filipe, Nogueira-Rodrigues Joana, Pinto-Costa Rita, Peters Luanne Laurel, Brites Pedro, Sousa Mónica Mendes
Nerve Regeneration Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; ICBAS, Universidade do Porto, 4050-313 Porto, Portugal.
Advanced Light Microscopy Unit, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
Cell Rep. 2016 Apr 19;15(3):490-498. doi: 10.1016/j.celrep.2016.03.047. Epub 2016 Apr 7.
The actin-binding protein adducin was recently identified as a component of the neuronal subcortical cytoskeleton. Here, we analyzed mice lacking adducin to uncover the function of this protein in actin rings. α-adducin knockout mice presented progressive axon enlargement in the spinal cord and optic and sciatic nerves, followed by axon degeneration and loss. Using stimulated emission depletion super-resolution microscopy, we show that a periodic subcortical actin cytoskeleton is assembled in every neuron type inspected including retinal ganglion cells and dorsal root ganglia neurons. In neurons devoid of adducin, the actin ring diameter increased, although the inter-ring periodicity was maintained. In vitro, the actin ring diameter adjusted as axons grew, suggesting the lattice is dynamic. Our data support a model in which adducin activity is not essential for actin ring assembly and periodicity but is necessary to control the diameter of both actin rings and axons and actin filament growth within rings.
肌动蛋白结合蛋白内收蛋白最近被鉴定为神经元皮质下细胞骨架的一个组成部分。在此,我们分析了缺乏内收蛋白的小鼠,以揭示该蛋白在肌动蛋白环中的功能。α-内收蛋白基因敲除小鼠在脊髓、视神经和坐骨神经中出现渐进性轴突增粗,随后轴突退化和丧失。使用受激发射损耗超分辨率显微镜,我们发现,在包括视网膜神经节细胞和背根神经节神经元在内的每种检查的神经元类型中,都组装了周期性的皮质下肌动蛋白细胞骨架。在缺乏内收蛋白的神经元中,肌动蛋白环直径增加,尽管环间周期性得以维持。在体外,随着轴突生长,肌动蛋白环直径会调整,这表明晶格是动态的。我们的数据支持这样一种模型,即内收蛋白活性对于肌动蛋白环的组装和周期性并非必不可少,但对于控制肌动蛋白环和轴突的直径以及环内肌动蛋白丝的生长是必要的。